The aim of this work is to investigate the mechanisms controlling the expression of a multi-gene family, namely the class I MHC genes. The miniature swine has been chosen as an experimental system because there are only 7 members of the family. Of these 6 have been isolated. To address the question of the molecular regulation of the expression of the class I MHC genes, two approaches have been taken: 1) analysis of in vivo patterns of expression in a variety of tissues and in transfected mouse L cells and 2) characterization of regulatory elements associated with these genes. Three categories of MHC genes have been identified this way: 1) A set of closely related genes which are expressed in L cells and in nearly all somatic tissues, although at different levels. These genes encode products which are expressed on the cell surface and are able to bind a monoclonal antibody which recognizes a common determinant, also found on classical transplantation antigens. 2) A distantly related gene which is expressed both in L cells and in vivo but whose pattern of expression is distinct from that of transplantation antigens. 3) A set of genes which is not expressed in L cells. Regulatory sequences within one of the transplantation antigen genes have been identified by generating a series of 5' end deletion mutants. The transcriptional promoter has been identified and the interferon-responsive element mapped to this region. No classical enhancer element has been identified in any segment of the gene.